WO1993009772A1 - Drug for hepatic diseases - Google Patents
Drug for hepatic diseases Download PDFInfo
- Publication number
- WO1993009772A1 WO1993009772A1 PCT/JP1992/001486 JP9201486W WO9309772A1 WO 1993009772 A1 WO1993009772 A1 WO 1993009772A1 JP 9201486 W JP9201486 W JP 9201486W WO 9309772 A1 WO9309772 A1 WO 9309772A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hepatitis
- hepatic
- dha
- drug
- liver
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
Definitions
- the present invention relates to an agent for liver disease having docosahexanoic acid or a derivative thereof as an active ingredient, particularly an agent for improving liver function and an anti-hepatitis agent.
- Docosahexaenoic acid or a derivative thereof is used as a mixed composition, for example, a therapeutic agent for diabetic complications (JP-A-60-248610), a therapeutic agent for hemorrhoids (JP-A-61-24518), a lipoxygenase metabolic stimulant (Special 63-230632), a brain function improving agent (JP-A-1-27982), an anticancer agent (JP-A-1-153629), a therapeutic agent for cystic kidney (JP-A-2-235811), and an antiarrhythmic agent (JP-A-2-35811). 4-29928).
- a therapeutic agent for diabetic complications JP-A-60-248610
- a therapeutic agent for hemorrhoids JP-A-61-24518
- a lipoxygenase metabolic stimulant Special 63-230632
- JP-A-1-153629 JP-A-1-153629
- cystic kidney JP-A-2-235811
- Polyphenophosphatidylcholine products are used as general agents for liver disease, and mevinolin and mevallotin compounds are used as agents that inhibit cholesterol biosynthesis. Cholesterol in serum is removed. Higher unsaturated fatty acids, such as linoleic acid and linolenic acid, have been widely known as substances that prevent arteriosclerosis.
- higher unsaturated fatty acids are substances whose properties can be said to be effective for the first time after taking them for a long time to prevent arteriosclerosis, etc. Without a doubt, its mild effects are only highlighted.
- liver function deterioration that is, cirrhosis, liver cancer, hepatitis, fatty liver, and various other liver diseases are pointed out, including cholesterol removal. Drugs for improving liver function were desired.
- hepatitis virus and various toxic substances cause hepatocellular destruction.
- fulminant hepatitis has nausea, vomiting, and malaise compared to normal hepatitis, high fever, increased white blood cell count, strong CRP, and gangrene may worsen rapidly. Known as fatal. Even if it does not lead to premature death, the number of cases ranging from chronic hepatitis to cirrhosis and hepatocellular carcinoma is extremely large, which is a social problem.
- hepatitis therapy which is an adjunct to treatment, is mainly used, and there is currently no effective hepatitis treatment agent or hepatitis induction inhibitor with no side effects.
- an object of the present invention is to provide a treatment and prevention effect for liver disease with low toxicity, early improvement of liver function, and treatment and prevention of hepatitis (fulminant hepatitis), liver cirrhosis, hepatocellular carcinoma, liver failure and the like. It is intended to provide a drug that is effective for the future. Disclosure of the invention
- the present inventors have been conducting research on the constituents of marine organisms, mainly fishes, for many years.
- liver function is improved by the fluidity, flexibility, and enhancement of the lipid bilayer of the liver raker membrane and microsomes that are intracellular granules.
- the ratio of cholesterol to phospholipid, a component of this lipid bilayer, is It is known that the smaller, the higher the fluidity.
- the agent for liver disease of the present invention contains docosahexaenoic acid and its derivative (DHA) as active ingredients.
- DHA include DHA choline compounds, DHA nicotinic acid compounds, and DHA amino acid compounds, including DHA, DHA ester, DHA glyceride-, and DHA phospholipid, as well as water-soluble DHA choline compounds.
- DHA triglyceride DHA triglyceride. This substance has a strong anti-hepatitis activity, and is particularly effective for treatment and prevention of hepatitis (fulminant hepatitis), cirrhosis, hepatocellular carcinoma, liver failure, etc. Is expected.
- the DHA used in the present invention is commercially available and can be extracted from animals, algae and microorganisms in the natural world by known methods.
- the dose of DHA which is an active ingredient of the agent for liver disease of the present invention, is preferably 0.1 to 50 gZday, more preferably 0.5 to 10 g / day.
- oral administration intravenous administration, enteral administration and the like can be performed.
- oral administration it can be adjusted to tablets, capsules, granules, powders, liquids, etc.
- parenteral administration it can be adjusted to subcutaneous, intramuscular, intravenous injections, suppositories, tablets and the like.
- As the carrier for baking commonly used emulsifiers, thorns, binders, lubricants, colored thorns and the like can be used.
- Excipients include, for example, lactose, sucrose, starch, tafflek, magnesium stearate, crystalline cellulose, methylcellulose, carboxymethiflecellulose, glycerin, sodium alginate, gum arabic, etc.
- examples thereof include polyvinyl alcohol, polyvinyl ether, ethyl cellulose, gum arabic, sierrank, sucrose, etc., and other conventional coloring agents, disintegrating agents, etc.
- the tablets may be coated by a generally known method.
- the liquid preparation may be an aqueous or oily suspension, emulsifier, solution, syrup, elixir or the like, and is prepared by a commonly used method.
- emulsifier DHA acids of the present invention P H buffers, stabilizers, isotonic agents, adding a local anesthetic, etc., subcutaneously by a conventional method, intramuscular, intravenous injections Can be manufactured.
- a base for producing suppositories for example, an oily base such as cocoa butter, polyethylene glycol, lanolin, fatty acid triglyceride, and ditebzol can be used.
- oral administration is the most preferable for administration of DHA, but when used as a soft capsule that is widely used, it is enough to enclose DHA alone, and dl is used as an antioxidant.
- _ It can contain 0.1-0.3% of tocopherol or catechin, etc. 100-l, 000mg is appropriate for the content of 1 capsule.
- sa It is sufficient to form 0.5iiig of tocopherol (or catechin) as a soft capsule, or it can be used by mixing it with various food base materials—other foods and forming it as a general food or healthy food.
- the solution may be an amino acid compound of DHA, a diascorbic acid compound, or an aqueous or oily suspension, an emulsifier, a ribosome, etc., and a PH buffer, a stabilizer, an isotonic agent, a local anesthetic, etc. May be blended.
- DHA diascorbic acid compound
- a PH buffer a stabilizer
- an isotonic agent a local anesthetic, etc.
- docosahexaenoyl L-glutamate dinadium 100g, glycerin 25g, dl-—tocofurol O.lg is made up to 1000 ml by adding water and sterilized before use.
- Acute toxicity test Acute toxicity test
- Test animals ddY-N mice, 5 weeks old, 5 males and 5 females
- test mice were sacrificed at the end of the test and visually examined by necropsy. No abnormalities were found in the main organs of any of the males and females in the 1160, 1380, 1660, and 2000 mg Zkg groups. Best form to apply light
- Example 2 The same experiment as in Example 1 was performed by replacing the DHA triglyceride emulsion with an emulsion using DHA ethyl ester (DHA purity: 99%). As a result, the control hepatitis model rat died 100% within 24 hours, while the DHA ethyl ester-treated rat survived 75%.
- DHA purity: 99% DHA ethyl ester
- DHA is a protein that is also involved in cholesterol metabolism that is produced and eluted in plasma, and specifically metabolizes cholesterol accumulated in liver microsomes mainly due to a decrease or abnormality in metabolism, resulting in microsomal lipids. It is a promising therapeutic agent for liver function improvement for fatty liver, cirrhosis, etc., which restores membrane flexibility and stimulates enzymes and activities and significantly reduces triglycerides, which is currently difficult to completely cure. is there. -In addition, according to the present invention, chronic hepatitis, cirrhosis, hepatocellular carcinoma, hepatic failure, etc. An anti-hepatitis agent capable of inhibiting the induction of hepatitis, which is one of the causes, is provided.
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/087,708 US5436269A (en) | 1991-11-14 | 1992-11-13 | Method for treating hepatitis |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP32501991A JPH05139965A (ja) | 1991-11-14 | 1991-11-14 | 抗肝炎剤 |
JP3/325019 | 1991-11-14 | ||
JP4166724A JPH05339154A (ja) | 1992-06-03 | 1992-06-03 | 肝機能改善剤 |
JP4/166724 | 1992-06-03 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1993009772A1 true WO1993009772A1 (en) | 1993-05-27 |
Family
ID=26490998
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1992/001486 WO1993009772A1 (en) | 1991-11-14 | 1992-11-13 | Drug for hepatic diseases |
Country Status (3)
Country | Link |
---|---|
US (1) | US5436269A (ja) |
EP (1) | EP0567653A4 (ja) |
WO (1) | WO1993009772A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999012538A1 (fr) * | 1997-09-05 | 1999-03-18 | Otsuka Pharmaceutical Co., Ltd. | Composition, additif alimentaire, et procede bloquant l'accumulation des graisses par le foie |
EP1000883A1 (fr) * | 1998-11-13 | 2000-05-17 | Materiel Pour L'arboriculture Fruitiere (M.A.F.) S.A. | Dispositif de convoyage de produits, notamment de fruits |
US6562056B2 (en) | 1992-06-02 | 2003-05-13 | General Surgical Innovations, Inc. | Balloon device for use in surgery and method of use |
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US20040043013A1 (en) | 2000-12-28 | 2004-03-04 | Mccleary Edward Larry | Metabolic uncoupling therapy |
US20030144219A1 (en) | 2001-11-15 | 2003-07-31 | Phinney Stephen Dodge | Formulations and methods for treatment or amelioration of inflammatory conditions |
US7981915B2 (en) * | 2003-04-30 | 2011-07-19 | Beth Israel Deaconess Medical Center | Methods for modulating PPAR biological activity for the treatment of diseases caused by mutations in the CFTR gene |
CA2545752C (en) | 2003-11-12 | 2013-03-26 | Children's Medical Center Corporation | Treatment and prevention of liver disease associated with parenteral nutrition (pn) |
DE102004052697A1 (de) * | 2004-10-29 | 2006-05-04 | Haehner, Thomas, Dr. | Pharmazeutische Zubereitungen zur Behandlung von Folgen des Alkoholmissbrauchs, Hepatitis, Pankreatitis, Alzheimererkrankung, Morbus Parkinson, Diabetes, toxischen Nierenerkrankungen, Reperfusionsschäden, der Arteriosklerose sowie als Antidote gegen Umweltgifte und Medikamentenintoxikation |
US20060286199A1 (en) * | 2005-06-03 | 2006-12-21 | Marilou Laprise | Method and composition for increasing omega-3 lipid in milk |
DE102006019906A1 (de) * | 2006-04-28 | 2007-10-31 | Müller-Enoch, Dieter, Prof. Dr. | Verwendung von Verbindungen der Formel A-R-X oder deren pharmazeutisch akzeptable Salze zur Herstellung einer pharmazeutischen Zubereitung |
JP2010532418A (ja) * | 2007-06-29 | 2010-10-07 | マーテック バイオサイエンシーズ コーポレーション | 多価不飽和脂肪酸のエステルの製造方法および精製方法 |
WO2010040012A1 (en) * | 2008-10-01 | 2010-04-08 | Martek Biosciences Corporation | Compositions and methods for reducing triglyceride levels |
JP5934102B2 (ja) | 2009-10-30 | 2016-06-15 | レトロトップ、 インコーポレイテッドRetrotope, Inc. | Pufa誘導体による酸化ストレス障害の緩和 |
US20110200645A1 (en) * | 2010-02-18 | 2011-08-18 | Martek Biosciences Corporation | DHA Free Fatty Acid Emulsions |
WO2011103510A1 (en) * | 2010-02-18 | 2011-08-25 | Martek Biosciences Corporation | Dha ester emulsions |
US20110206741A1 (en) * | 2010-02-18 | 2011-08-25 | Martek Biosciences Corporation | DHA Triglyceride Emulsions |
EP2701697B1 (en) | 2011-04-26 | 2020-03-25 | Retrotope, Inc. | Oxidative retinal diseases |
EP3730135A1 (en) | 2011-04-26 | 2020-10-28 | Retrotope, Inc. | Impaired energy processing disorders and mitochondrial deficiency |
CA2834274C (en) | 2011-04-26 | 2021-08-03 | Retrotope, Inc. | Neurodegenerative disorders and muscle diseases implicating pufas |
EP2701698B1 (en) | 2011-04-26 | 2020-12-23 | Retrotope, Inc. | Disorders implicating pufa oxidation |
RU2505289C2 (ru) * | 2011-11-07 | 2014-01-27 | Общество С Ограниченной Ответственностью "Консорциум-Пик" | Фармацевтическая композиция на основе растительной докозагексаеновой кислоты для лечения и профилактики заболеваний печени |
US9610302B2 (en) | 2013-12-05 | 2017-04-04 | Buriva, LLC. | Composition containing phospholipid-DHA and B vitamins |
US9216199B2 (en) | 2013-12-05 | 2015-12-22 | Buriva, LLC | Nutritional supplement containing phospholipid-DHA derived from eggs |
US9549937B2 (en) | 2013-12-05 | 2017-01-24 | Burvia, LLC. | Composition containing phospholipid-DHA and folate |
US9233114B2 (en) | 2013-12-05 | 2016-01-12 | Buriva, LLC | Dietary supplement containing phospholipid-DHA derived from eggs |
CA3005983A1 (en) | 2015-11-23 | 2017-06-01 | Retrotope, Inc. | Site-specific isotopic labeling of 1,4-diene systems |
US11324697B2 (en) | 2017-08-10 | 2022-05-10 | The Children's Medical Center Corporation | Methods and compositions relating to emulsions comprising fish oil and/or omega-3 fatty acids |
AU2021224854A1 (en) | 2020-02-21 | 2022-10-06 | Biojiva Llc | Processes for isotopic modification of polyunsaturated fatty acids and derivatives thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS56122312A (en) * | 1980-02-29 | 1981-09-25 | Kagakuhin Kensa Kyokai | Hepatic cholesterol-lowering agent (hepatic decholesterolizing agent) |
JPS63297342A (ja) * | 1987-05-28 | 1988-12-05 | Nisshin Oil Mills Ltd:The | 合成油脂ならびにこれを含有する脂肪乳剤輸液および経腸栄養剤 |
JPH02200165A (ja) * | 1989-01-31 | 1990-08-08 | Snow Brand Milk Prod Co Ltd | 血清脂質の改善作用を有する栄養剤組成物 |
Family Cites Families (7)
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GB1240513A (en) * | 1968-09-13 | 1971-07-28 | Ono Pharmaceutical Co | Poly-unsaturated fatty acid ester composition and its preparation |
US4513008A (en) * | 1982-07-30 | 1985-04-23 | The Vinoxen Company, Inc. | Virucidal compositions and therapy |
US4607052A (en) * | 1983-04-15 | 1986-08-19 | Roussel-Uclaf | Triglycerides, dietetic and therapeutical applications and compositions containing them |
AU4595985A (en) * | 1984-08-10 | 1986-02-13 | Sentrachem Limited | Cancer treatment |
US4692280A (en) * | 1986-12-01 | 1987-09-08 | The United States Of America As Represented By The Secretary Of Commerce | Purification of fish oils |
GB2218904A (en) * | 1988-05-27 | 1989-11-29 | Renafield Limited | Pharmaceutical composition based on high-concentration esters of docosahexaenoic acid |
GB8813766D0 (en) * | 1988-06-10 | 1988-07-13 | Efamol Holdings | Essential fatty acid compositions |
-
1992
- 1992-11-13 WO PCT/JP1992/001486 patent/WO1993009772A1/ja not_active Application Discontinuation
- 1992-11-13 US US08/087,708 patent/US5436269A/en not_active Expired - Fee Related
- 1992-11-13 EP EP19920923408 patent/EP0567653A4/en not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS56122312A (en) * | 1980-02-29 | 1981-09-25 | Kagakuhin Kensa Kyokai | Hepatic cholesterol-lowering agent (hepatic decholesterolizing agent) |
JPS63297342A (ja) * | 1987-05-28 | 1988-12-05 | Nisshin Oil Mills Ltd:The | 合成油脂ならびにこれを含有する脂肪乳剤輸液および経腸栄養剤 |
JPH02200165A (ja) * | 1989-01-31 | 1990-08-08 | Snow Brand Milk Prod Co Ltd | 血清脂質の改善作用を有する栄養剤組成物 |
Non-Patent Citations (1)
Title |
---|
See also references of EP0567653A4 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6562056B2 (en) | 1992-06-02 | 2003-05-13 | General Surgical Innovations, Inc. | Balloon device for use in surgery and method of use |
US6565589B1 (en) | 1992-06-02 | 2003-05-20 | General Surgical Innovations, Inc. | Balloon device for use in surgery and method of use |
WO1999012538A1 (fr) * | 1997-09-05 | 1999-03-18 | Otsuka Pharmaceutical Co., Ltd. | Composition, additif alimentaire, et procede bloquant l'accumulation des graisses par le foie |
US6468556B1 (en) | 1997-09-05 | 2002-10-22 | Otsuka Pharmaceutical Co., Ltd. | Liver fat accumulation inhibitory composition, food additive for liver fat accumulation, inhibition, and method of inhibiting liver fat accumulation |
EP1000883A1 (fr) * | 1998-11-13 | 2000-05-17 | Materiel Pour L'arboriculture Fruitiere (M.A.F.) S.A. | Dispositif de convoyage de produits, notamment de fruits |
FR2785892A1 (fr) * | 1998-11-13 | 2000-05-19 | Materiel Arboriculture | Dispositif de convoyage de produits, notamment de fruits |
US6234297B1 (en) | 1998-11-13 | 2001-05-22 | Materiel Pour L'arboriculture Fruitiere | Device for conveying products, in particular fruit |
Also Published As
Publication number | Publication date |
---|---|
EP0567653A1 (en) | 1993-11-03 |
US5436269A (en) | 1995-07-25 |
EP0567653A4 (en) | 1994-06-01 |
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